1α,25-Dihydroxyvitamin D₃ up-regulates expression of the osteoclast integrin α_vβ₃

Osteoclast precursors selectively attach to bone and differentiate into multinucleated cells that function to remodel and resorb it. We have shown previously that attachment of osteoclasts to bone and subsequent resorption are mediated by the integrin α_vβ₃. 1α,25-Dihydroxyvitamin D₃ (1,25-(OH)₂D₃) enhances osteoclast precursor differentiation in vivo by mechanisms that are still not clearly understood but entail enhanced attachment of cells to bone. This observation raises the possibility that at least one component of vitamin D-induced osteoclast precursor differentiation involves modulation of integrin expression. To test if the steroid modulates the osteoclast integrin α_vβ₃ (the vitronectin receptor), we examined the effects of 1,25-(OH)₂D₃ on transcription of the α_v gene as well as surface expression and function of α_vβ₃, in chicken osteoclast precursors. Treatment of the cells with 1,25-(OH)₂D₃ led to a progressive dose-dependent increase in steady state α_v mRNA levels with enhanced expression evident within 24 h. The effect was receptor-mediated as indicated by the effects of other vitamin D analogs. The increase in α_v mRNA levels did not reflect decreased message degradation but, as demonstrated by nuclear run-on experiments, was due to accelerated rates of transcription. Most importantly, induction of α_v mRNA by 1,25-(OH)₂D₃ was mirrored by higher levels of expression of α_vβ₃ on the cell surface, as well enhanced attachment to its substrate, vitronectin.